Proteomics

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Tear proteomics reveals the molecular basis of the efficacy of human recombinant nerve growth factor treatment for Neurotrophic Keratopathy


ABSTRACT: Neurotrophic Keratopathy (NK),classified as an orphan disease (ORPHA137596), is a rare degenerative corneal disease characterized by epithelial instability and decreased corneal sensitivity caused by the damage to the corneal nerves. The administration of human recombinant nerve growth factor (rhNGF) eye drops, as a licensed-in-Europe specific medication for treatment of moderate and severe NK, has added promising perspectives to the management of this disorder by providing a valid alternative to the neurotization surgery. However, few studies have been conducted to the molecular mechanism underlying the response to the treatment. Here, we carried out tears proteomics to highlight the protein expression during pharmacological treatment of NK. Our data emphasized a proteome modulation duringrhNGF treatment related to an increase in DNA synthesis, an activation ofboth BDNF signaland IL6 receptor.Furthermore, the amount of neuronal Extracellular Vesicles EVs (CD171+)correlated with the EVs carrying IL6R (CD126+) togetherassociated to the inflammatory EVs (CD45+) in tears. Such scenario determined drug response, confirmed by an in vivo confocal microscopy analysis, showing an increase in length, density and number of nerve fiber branches during treatment. In summary, rhNGF treatment seems to determine an inflammatory micro-environment, mediated by functionalized EVs, defining the drug response by stimulating protein synthesis and fiber regeneration.

INSTRUMENT(S): maXis

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Neurotrophic Keratoconjunctivitis

SUBMITTER: Maria Concetta Cufaro  

LAB HEAD: Piero Del Boccio

PROVIDER: PXD025408 | Pride | 2022-02-14

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
POOL_t0_tears_NGF_01_A3_01_11837.d.7z Other
POOL_t0_tears_NGF_02_A3_01_11843.d.7z Other
POOL_t0_tears_NGF_03_A3_01_11849.d.7z Other
POOL_t4_tears_NGF_01_A4_01_11839.d.7z Other
POOL_t4_tears_NGF_02_A4_01_11845.d.7z Other
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Publications

Tear proteomics reveals the molecular basis of the efficacy of human recombinant nerve growth factor treatment for Neurotrophic Keratopathy.

Pieragostino Damiana D   Lanzini Manuela M   Cicalini Ilaria I   Cufaro Maria Concetta MC   Damiani Verena V   Mastropasqua Leonardo L   De Laurenzi Vincenzo V   Nubile Mario M   Lanuti Paola P   Bologna Giuseppina G   Agnifili Luca L   Del Boccio Piero P  

Scientific reports 20220124 1


Neurotrophic Keratopathy (NK), classified as an orphan disease (ORPHA137596), is a rare degenerative corneal disease characterized by epithelial instability and decreased corneal sensitivity caused by the damage to the corneal nerves. The administration of human recombinant nerve growth factor (rhNGF) eye drops, as a licensed-in-Europe specific medication for treatment of moderate and severe NK, has added promising perspectives to the management of this disorder by providing a valid alternative  ...[more]

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